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Citations to this article

Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells
Robert Besch, … , Simon Rothenfusser, Gunther Hartmann
Robert Besch, … , Simon Rothenfusser, Gunther Hartmann
Published July 20, 2009
Citation Information: J Clin Invest. 2009;119(8):2399-2411. https://doi.org/10.1172/JCI37155.
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Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells

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Abstract

The retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I– and MDA-5–initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I– and MDA-5–mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis.

Authors

Robert Besch, Hendrik Poeck, Tobias Hohenauer, Daniela Senft, Georg Häcker, Carola Berking, Veit Hornung, Stefan Endres, Thomas Ruzicka, Simon Rothenfusser, Gunther Hartmann

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Combined Adjuvant of Poly I:C Improves Antitumor Effects of CAR-T Cells
S Di, M Zhou, Z Pan, R Sun, M Chen, H Jiang, B Shi, H Luo, Z Li
Frontiers in Oncology 2019
Knockdown of IGF-1R Triggers Viral RNA Sensor MDA5- and RIG-I-Mediated Mitochondrial Apoptosis in Colonic Cancer Cells
SQ Wang, XY Yang, XF Yu, SX Cui, XJ Qu
Molecular Therapy — Nucleic Acids 2019
RIG-I activating immunostimulatory RNA boosts the efficacy of anticancer vaccines and synergizes with immune checkpoint blockade
S Heidegger, D Kreppel, M Bscheider, F Stritzke, T Nedelko, A Wintges, S Bek, JC Fischer, T Graalmann, U Kalinke, F Bassermann, T Haas, H Poeck
EBioMedicine 2019
Requirement of the transcription factor YB-1 for maintaining the stemness of cancer stem cells and reverting differentiated cancer cells into cancer stem cells
F Yang, P Cui, Y Lu, X Zhang
Stem Cell Research & Therapy 2019
The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
L Zhang, Q Xia, W Li, Q Peng, H Yang, X Lu, G Wang
Arthritis Research & Therapy 2019
A non‐death function of the mitochondrial apoptosis apparatus in immunity
D Brokatzky, B Dörflinger, A Haimovici, A Weber, S Kirschnek, J Vier, A Metz, J Henschel, T Steinfeldt, IE Gentle, G Häcker
The EMBO Journal 2019
RNase L Induces Expression of A Novel Serine/Threonine Protein Kinase, DRAK1, to Promote Apoptosis
P Manivannan, V Reddy, S Mukherjee, KN Clark, K Malathi
International journal of molecular sciences 2019
An optimized retinoic acid-inducible gene I agonist M8 induces immunogenic cell death markers in human cancer cells and dendritic cell activation
L Castiello, A Zevini, E Vulpis, M Muscolini, M Ferrari, E Palermo, G Peruzzi, C Krapp, M Jakobsen, D Olagnier, A Zingoni, A Santoni, J Hiscott
Cancer Immunology, Immunotherapy 2019
DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer
SR Paludan, LS Reinert, V Hornung
Nature Reviews Immunology 2019
Erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-κB and p38 MAPK pathway.
Liang X, Huang Y, Pan X, Hao Y, Chen X, Jiang H, Li J, Zhou B, Yang Z
Journal of Pharmaceutical Analysis 2019
Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses.
Jiang X, Muthusamy V, Fedorova O, Kong Y, Kim DJ, Bosenberg M, Pyle AM, Iwasaki A
Journal of Experimental Medicine 2019
RIG-I-based immunotherapy enhances survival in preclinical AML models and sensitizes AML cells to checkpoint blockade.
Ruzicka M, Koenig LM, Formisano S, Boehmer DFR, Vick B, Heuer EM, Meinl H, Kocheise L, Zeitlhöfler M, Ahlfeld J, Kobold S, Endres S, Subklewe M, Duewell P, Schnurr M, Jeremias I, Lichtenegger FS, Rothenfusser S
Leukemia 2019
High RIG-I expression in ovarian cancer associates with an immune-escape signature and poor clinical outcome.
Wolf D, Fiegl H, Zeimet AG, Wieser V, Marth C, Sprung S, Sopper S, Hartmann G, Reimer D, Boesch M
International Journal of Cancer 2019
Murine Models of Hepatitis A Virus Infection
A Hirai-Yuki, JK Whitmire, M Joyce, DL Tyrrell, SM Lemon
Cold Spring Harbor Perspectives in Medicine 2018
Harnessing RIG-I and intrinsic immunity in the tumor microenvironment for therapeutic cancer treatment
DL Elion, RS Cook
Oncotarget 2018
Environmentally Triggerable Retinoic Acid-Inducible Gene I Agonists Using Synthetic Polymer Overhangs
CR Palmer, ME Jacobson, O Fedorova, AM Pyle, JT Wilson
Bioconjugate Chemistry 2018
Fascin1 suppresses RIG-I–like receptor signaling and interferon-β production by associating with IκB kinase ϵ (IKKϵ) in colon cancer
T Matsumura, S Hida, M Kitazawa, C Fujii, A Kobayashi, M Takeoka, S Taniguchi, S Miyagawa
The Journal of biological chemistry 2018
Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies
S Iurescia, D Fioretti, M Rinaldi
Frontiers in immunology 2018
Low doses of LPS exacerbate the inflammatory response and trigger death on TLR3-primed human monocytes
M Monguió-Tortajada, M Franquesa, MR Sarrias, FE Borràs
Cell Death and Disease 2018
Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed by solution-based analysis
N Shah, SA Beckham, JA Wilce, MC Wilce
Nucleic Acids Research 2018
Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in�vitro
H Yoshino, M Iwabuchi, Y Kazama, M Furukawa, I Kashiwakura
Oncology Letters 2018
Nanoparticle Delivery of RIG-I Agonist Enables Effective and Safe Adjuvant Therapy in Pancreatic Cancer
M Das, L Shen, Q Liu, TJ Goodwin, L Huang
Molecular Therapy 2018
Anti-tumor macrophages activated by ferumoxytol combined or surface-functionalized with the TLR3 agonist poly (I : C) promote melanoma regression
J zhao, Z Zhang, Y Xue, G Wang, Y Cheng, Y Pan, S Zhao, Y Hou
Theranostics 2018
ADAR1‐mediated RNA editing is required for thymic self‐tolerance and inhibition of autoimmunity
T Nakahama, Y Kato, JI Kim, T Vongpipatana, Y Suzuki, CR Walkley, Y Kawahara
EMBO reports 2018
Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma
LL Lin, CC Huang, MT Wu, WM Hsu, JH Chuang
Cancer Science 2018
Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies.
Lee J, Park EB, Min J, Sung SE, Jang Y, Shin JS, Chun D, Kim KH, Hwang J, Lee MK, Go YY, Kwon D, Kim M, Kang SJ, Choi BS
Nucleic Acids Research 2018
The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond
C Peteranderl, S Herold
Frontiers in immunology 2017
MDA5 Induces a Stronger Interferon Response than RIG-I to GCRV Infection through a Mechanism Involving the Phosphorylation and Dimerization of IRF3 and IRF7 in CIK Cells
Q Wan, C Yang, Y Rao, Z Liao, J Su
Frontiers in immunology 2017
Promising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways
K Li, S Qu, X Chen, Q Wu, M Shi
International journal of molecular sciences 2017
Caspases control antiviral innate immunity
H Chen, X Ning, Z Jiang
Cellular and Molecular Immunology 2017
Picornaviruses and Apoptosis: Subversion of Cell Death
SN Croft, EJ Walker, R Ghildyal, DE Griffin, RJ Collier
mBio 2017
The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation
Y Dou, HC Yim, CD Kirkwood, BR Williams, AJ Sadler
The EMBO Journal 2017
Xenopus -FV3 host-pathogen interactions and immune evasion
R Jacques, ES Edholm, S Jazz, TL Odalys, DJ Francisco
Virology 2017
Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells
G Raicevic, M Najar, H Busser, E Crompot, D Bron, M Toungouz, L Lagneaux
Scientific Reports 2017
Differential Induction of Immunogenic Cell Death and Interferon Expression in Cancer Cells by Structured ssRNAs
J Lee, Y Lee, L Xu, R White, BA Sullenger
Molecular Therapy 2017
The role of alternative polyadenylation in the antiviral innate immune response
X Jia, S Yuan, Y Wang, Y Fu, Y Ge, Y Ge, X Lan, Y Feng, F Qiu, P Li, S Chen, A Xu
Nature Communications 2017
Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways
A Zevini, D Olagnier, J Hiscott
Trends in Immunology 2017
MAVS-dependent host species range and pathogenicity of human hepatitis A virus
A Hirai-Yuki, L Hensley, DR McGivern, O Gonzalez-Lopez, A Das, H Feng, L Sun, JE Wilson, F Hu, Z Feng, W Lovell, I Misumi, JP Ting, S Montgomery, J Cullen, JK Whitmire, SM Lemon
Science 2016
Recombinant Ranaviruses for Studying Evolution of Host–Pathogen Interactions in Ectothermic Vertebrates
J Robert, J Jancovich
Viruses 2016
Targeting polyIC to EGFR over-expressing cells using a dsRNA binding protein domain tethered to EGF
N Edinger, M Lebendiker, S Klein, M Zigler, Y Langut, A Levitzki, V Franciscis
PloS one 2016
Activation of the MDA-5-IPS-1 Viral Sensing Pathway Induces Cancer Cell Death and Type I IFN-Dependent Antitumor Immunity
X Yu, H Wang, X Li, C Guo, F Yuan, PB Fisher, XY Wang
Cancer research 2016
2′Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors
Y Lee, JH Urban, L Xu, BA Sullenger, J Lee
Nucleic Acid Therapeutics (Formerly Oligonucleotides) 2016
RIG-I activation induces the release of extracellular vesicles with antitumor activity
J Daßler-Plenker, KS Reiners, JG van Boorn, HP Hansen, B Putschli, S Barnert, C Schuberth-Wagner, R Schubert, T Tüting, M Hallek, M Schlee, G Hartmann, EP von Strandmann, C Coch
OncoImmunology 2016
Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages
TC Ma, RH Zhou, X Wang, JL Li, M Sang, L Zhou, K Zhuang, W Hou, DY Guo, WZ Ho
Scientific Reports 2016
Hitting the right button: MAVS-mediated defense against HAV infection
PA Knolle
Cell Research 2016
Anti-apoptotic Bcl-XL but not Mcl-1 contributes to protection against virus-induced apoptosis
M Ohmer, A Weber, G Sutter, K Ehrhardt, A Zimmermann, G Häcker
Cell Death and Disease 2016
Nucleic Acid Immunity.
Hartmann G
Advances in immunology 2016
Discriminating self from non-self in nucleic acid sensing
Schlee M, Hartmann G
Nature reviews. Immunology 2016
Nature Biotechnology's academic spinouts of 2015.
Bouchie A, DeFrancesco L
Nature Biotechnology 2016
Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands.
Klein JC, Wild CA, Lang S, Brandau S
Cancer Immunology, Immunotherapy 2016
Overexpression of the Transcription Factor Sp1 Activates the OAS-RNAse L-RIG-I Pathway
V Dupuis-Maurin, L Brinza, J Baguet, E Plantamura, S Schicklin, S Chambion, C Macari, M Tomkowiak, E Deniaud, Y Leverrier, J Marvel, MC Michallet, X Chen
PloS one 2015
Transfected Poly(I:C) Activates Different dsRNA Receptors, Leading to Apoptosis or Immunoadjuvant Response in Androgen-independent Prostate Cancer Cells
S Palchetti, D Starace, PD Cesaris, A Filippini, E Ziparo, A Riccioli
The Journal of biological chemistry 2015
Type I Interferon Response Is Delayed in Human Astrovirus Infections
S Guix, A Pérez-Bosque, L Miró, M Moretó, A Bosch, RM Pintó, K Li
PloS one 2015
Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus
L Grayfer, FD Andino, J Robert, G McFadden
Journal of virology 2015
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts
D Roulois, H Loo Yau, R Singhania, Y Wang, A Danesh, SY Shen, H Han, G Liang, PA Jones, TJ Pugh, C OBrien, DD De Carvalho
Cell 2015
Immune- and miRNA-response to recombinant interferon beta-1a: a biomarker evaluation study to guide the development of novel type I interferon- based therapies
M Coenen, AV Hinze, M Mengel, C Fuhrmann, B Lüdenbach, J Zimmermann, V Dykstra, R Fimmers, R Viviani, J Stingl, S Holdenrieder, M Müller, G Hartmann, C Coch
BMC Pharmacology and Toxicology 2015
Targeted activation of melanoma differentiation-associated protein 5 (MDA5) for immunotherapy of pancreatic carcinoma
P Duewell, E Beller, SV Kirchleitner, T Adunka, H Bourhis, J Siveke, D Mayr, S Kobold, S Endres, M Schnurr
OncoImmunology 2015
RNase L Cleavage Products Promote Switch from Autophagy to Apoptosis by Caspase-Mediated Cleavage of Beclin-1
M Siddiqui, S Mukherjee, P Manivannan, K Malathi
International journal of molecular sciences 2015
Characterization of Frog Virus 3 knockout mutants lacking putative virulence genes
FD Andino, L Grayfer, G Chen, VG Chinchar, ES Edholm, J Robert
Virology 2015
RIPK1 and NF- B signaling in dying cells determines cross-priming of CD8+ T cells
N Yatim, H Jusforgues-Saklani, S Orozco, O Schulz, RB da Silva, CR Sousa, DR Green, A Oberst, ML Albert
Science 2015
Periodic-shRNA molecules are capable of gene silencing, cytotoxicity and innate immune activation in cancer cells
KE Shopsowitz, C Wu, G Liu, EC Dreaden, PT Hammond
Nucleic Acids Research 2015
Oncolytic Sendai virus-based virotherapy for cancer: recent advances
Y Kaneda, K Saga
Oncolytic Virotherapy 2015
In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-XL and Mcl-1 but in the absence of active BH3-only proteins
D Senft, A Weber, F Saathoff, C Berking, MV Heppt, C Kammerbauer, S Rothenfusser, S Kellner, Z Kurgyis, R Besch, G Häcker
Cell Death and Disease 2015
MDA5 complements TLR3 in suppression of neuroblastoma
WM Hsu, CC Huang, HY Lee, PY Wu, MT Wu, HC Chuang, LL Lin, JH Chuang
Oncotarget 2015
IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons-dependent and -independent anticancer activity
S Kumar, H Ingle, S Mishra, RS Mahla, A Kumar, T Kawai, S Akira, A Takaoka, AA Raut, H Kumar
Cell Death and Disease 2015
Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity
Errett JS, Gale M
Virologica Sinica 2015
Anti-angiogenic efficacy of 5′-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs
Yuan D, Xia M, Meng G, Xu C, Song Y, Wei J
Oncotarget 2015
How do viruses control mitochondria-mediated apoptosis?
Neumann S, El Maadidi S, Faletti L, Haun F, Labib S, Schejtman A, Maurer U, Borner C
Virus Research 2015
Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing.
Terasawa Y, Hotani T, Katayama Y, Tachibana M, Mizuguchi H, Sakurai F
Cancer Gene Therapy 2015
The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice.
Ginzel M, Yu Y, Klemann C, Feng X, von Wasielewski R, Park JK, Hornef MW, Torow N, Vieten G, Ure BM, Kuebler JF, Lacher M
Pediatric Research 2015
Intracellular Poly(I:C) Initiated Gastric Adenocarcinoma Cell Apoptosis and Subsequently Ameliorated NK Cell Functions
J Qu, Z Hou, Q Han, W Jiang, C Zhang, Z Tian, J Zhang
Journal of Interferon & Cytokine Research 2014
Implementing combinatorial immunotherapeutic regimens against cancer
D Wolf, A Heine, P Brossart
OncoImmunology 2014
RIG-I Enhanced Interferon Independent Apoptosis upon Junin Virus Infection
OA Kolokoltsova, AM Grant, C Huang, JK Smith, AL Poussard, B Tian, AR Brasier, CJ Peters, CT Tseng, JC de la Torre, S Paessler
PloS one 2014
Hybridization of poly(rI) with poly(rC) adsorbed to the carbon nanotube surface
MV Karachevtsev, GO Gladchenko, VS Leontiev, VA Karachevtsev
Nanoscale research letters 2014
The untranslated regions of classic swine fever virus RNA trigger apoptosis
WL Hsu, CL Chen, SW Huang, CC Wu, IH Chen, M Nadar, YP Su, CH Tsai
PloS one 2014
Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections
L Wei, J Cui, Y Song, S Zhang, F Han, R Yuan, L Gong, P Jiao, M Liao
Veterinary Research 2014
Effects of ionizing radiation on retinoic acid-inducible gene-I-like receptors
H Yoshino, T Saitoh, M Kozakai, I Kashiwakura
Biomedical Reports 2014
Transfection of poly(I:C) can induce reactive oxygen species-triggered apoptosis and interferon-β-mediated growth arrest in human renal cell carcinoma cells via innate adjuvant receptors and the 2-5A system
N Harashima, T Minami, H Uemura, M Harada
Molecular Cancer 2014
Mouse Embryonic Stem Cells Have Underdeveloped Antiviral Mechanisms That Can Be Exploited for the Development of mRNA-Mediated Gene Expression Strategy
R Wang, C Teng, J Spangler, J Wang, F Huang, YL Guo
Stem Cells and Development 2014
Pancreatic Cancer-Specific Cell Death Induced In Vivo by Cytoplasmic-Delivered Polyinosine-Polycytidylic Acid
P Bhoopathi, BA Quinn, Q Gui, XN Shen, SR Grossman, SK Das, D Sarkar, PB Fisher, L Emdad
Cancer research 2014
Functional Role of Autophagy-Mediated Proteome Remodeling in Cell Survival Signaling and Innate Immunity
R Mathew, S Khor, SR Hackett, JD Rabinowitz, DH Perlman, E White
Molecular Cell 2014
RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8+ T cells
P Duewell, A Steger, H Lohr, H Bourhis, H Hoelz, SV Kirchleitner, MR Stieg, S Grassmann, S Kobold, JT Siveke, S Endres, M Schnurr
Cell Death and Differentiation 2014
Intratumoral Immunization: A New Paradigm for Cancer Therapy
A Marabelle, H Kohrt, C Caux, R Levy
Clinical cancer research 2014
Induction of immunogenic cell death by targeting RIG-I-like helicases in pancreatic cancer
M Schnurr, P Duewell
OncoImmunology 2014
TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo
G Gambara, M Desideri, A Stoppacciaro, F Padula, PD Cesaris, D Starace, A Tubaro, D Bufalo, A Filippini, E Ziparo, A Riccioli
Journal of Cellular and Molecular Medicine 2014
Tumor suppressor activity of RIG-I
XY Li, HZ Guo, J Zhu
Molecular & Cellular Oncology 2014
Cellular Uptake of Tile-Assembled DNA Nanotubes
S Kocabey, H Meinl, I MacPherson, V Cassinelli, A Manetto, S Rothenfusser, T Liedl, F Lichtenegger
Nanomaterials 2014
CIMT 2014: Next waves in cancer immunotherapy - Report on the 12th annual meeting of the Association for Cancer Immunotherapy: May 6–8 2014, Mainz, Germany
M Diken, S Boegel, C Grunwitz, LM Kranz, K Reuter, N de Roemer, F Vascotto, M Vormehr, S Kreiter
Human Vaccines & Immunotherapeutics 2014
SOX10 promotes melanoma cell invasion by regulating melanoma inhibitory activity.
Graf SA, Busch C, Bosserhoff AK, Besch R, Berking C
Journal of Investigative Dermatology 2014
Organelle-specific initiation of cell death.
Galluzzi L, Bravo-San Pedro JM, Kroemer G
Nature Cell Biology 2014
Innate adjuvant receptor Toll-like receptor 3 can promote breast cancer through cell surface.
Bondhopadhyay B, Moirangthem A, Basu A
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2014
The neural crest transcription factor Brn3a is expressed in melanoma and required for cell cycle progression and survival
T Hohenauer, C Berking, A Schmidt, S Haferkamp, D Senft, C Kammerbauer, S Fraschka, SA Graf, M Irmler, J Beckers, M Flaig, A Aigner, S Höbel, F Hoffmann, H Hermeking, S Rothenfusser, S Endres, T Ruzicka, R Besch
EMBO Molecular Medicine 2013
Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids
JR Viola, DF Rafael, E Wagner, R Besch, M Ogris
Journal of drug delivery 2013
Functional RIG-I-like receptors control the survival of mesenchymal stem cells
K Yang, J Wang, AP Xiang, X Zhan, Y Wang, M Wu, X Huang
Cell Death and Disease 2013
IL-27 enhances the expression of TRAIL and TLR3 in human melanomas and inhibits their tumor growth in cooperation with a TLR3 agonist poly(I:C) partly in a TRAIL-dependent manner
Y Chiba, I Mizoguchi, K Mitobe, K Higuchi, H Nagai, C Nishigori, J Mizuguchi, T Yoshimoto
PloS one 2013
Breaking tumor-induced immunosuppression with 5'-triphosphate siRNA silencing TGFβ and activating RIG-I
M Schnurr, P Duewell
OncoImmunology 2013
MAVS regulates apoptotic cell death by decreasing K48-linked ubiquitination of voltage-dependent anion channel 1
K Guan, Z Zheng, T Song, X He, C Xu, Y Zhang, S Ma, Y Wang, Q Xu, Y Cao, J Li, X Yang, X Ge, C Wei, H Zhong
Molecular and cellular biology 2013
The RIG-I/MAVS signaling pathway in cancer cell-selective apoptosis
Y Kaneda
OncoImmunology 2013
Dose dependent activation of retinoic acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma
J Hu, Y He, M Yan, C Zhu, W Ye, H Zhu, W Chen, C Zhang, Z Zhang
PloS one 2013
Codelivery of zoledronic acid and doublestranded RNA from core-shell nanoparticles
L Chen, Y Ding, Y Wang, X Liu, R Babu, W Ravis, W Yan
International Journal of Nanomedicine 2013
The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome
H Mitoma, S Hanabuchi, T Kim, M Bao, Z Zhang, N Sugimoto, YJ Liu
Immunity 2013
Hepatitis C Therapy With Interferon-  and Ribavirin Reduces CD4 T-Cell-Associated HIV-1 DNA in HIV-1/Hepatitis C Virus-Coinfected Patients
H Sun, MJ Buzon, A Shaw, RK Berg, XG Yu, S Ferrando-Martinez, M Leal, E Ruiz-Mateos, M Lichterfeld
The Journal of Infectious Diseases 2013
Cytosolic Sensing of Viruses
D Goubau, S Deddouche, CR e Sousa
Immunity 2013
Relevance of signaling molecules for apoptosis induction on influenza A virus replication
Iwai A, Shiozaki T, Miyazaki T
Biochemical and Biophysical Research Communications 2013
Type I IFN-mediated regulation of IL-1 production in inflammatory disorders
K Ludigs, V Parfenov, RA Pasquier, G Guarda
Cellular and Molecular Life Sciences 2012
The role of innate immune signals in antitumor immunity
M Jinushi
OncoImmunology 2012
Targeting pattern recognition receptors in cancer immunotherapy
N Goutagny, Y Estornes, U Hasan, S Lebecque, C Caux
Targeted Oncology 2012
Triggering of the dsRNA Sensors TLR3, MDA5, and RIG-I Induces CD55 Expression in Synovial Fibroblasts
ON Karpus, KM Heutinck, PJ Wijnker, PP Tak, J Hamann
PloS one 2012
The Molecular Effects of a Polymorphism in the 5′UTR of Solute Carrier Family 44, Member 5 that Is Associated with Birth Weight in Holsteins
M Sugimoto, T Watanabe, Y Sugimoto
PloS one 2012
Selective Induction of Cell Death in Melanoma Cell Lines through Targeting of Mcl-1 and A1
D Senft, C Berking, SA Graf, C Kammerbauer, T Ruzicka, R Besch
PloS one 2012
IκB Kinase ε-Dependent Phosphorylation and Degradation of X-Linked Inhibitor of Apoptosis Sensitizes Cells to Virus-Induced Apoptosis
P Nakhaei, Q Sun, M Solis, T Mesplede, E Bonneil, S Paz, R Lin, J Hiscott
Journal of virology 2012
Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
S Chiba, M Baghdadi, H Akiba, H Yoshiyama, I Kinoshita, H Dosaka-Akita, Y Fujioka, Y Ohba, JV Gorman, JD Colgan, M Hirashima, T Uede, A Takaoka, H Yagita, M Jinushi
Nature Immunology 2012
Innate immune agonist, dsRNA, induces apoptosis in ovarian cancer cells and enhances the potency of cytotoxic chemotherapeutics
DN Van, CF Roberts, JD Marion, S Lépine, KB Harikumar, J Schreiter, CI Dumur, X Fang, S Spiegel, JK Bell
The FASEB Journal 2012
Mitochondrial antiviral signaling protein defect links impaired antiviral response and liver injury in steatohepatitis in mice
T Csak, A Dolganiuc, K Kodys, B Nath, J Petrasek, S Bala, D Lippai, G Szabo
Hepatology 2011
RIG-I– and MDA5-Initiated Innate Immunity Linked With Adaptive Immunity Accelerates β-Cell Death in Fulminant Type 1 Diabetes
K Aida, Y Nishida, S Tanaka, T Maruyama, A Shimada, T Awata, M Suzuki, H Shimura, S Takizawa, M Ichijo, D Akiyama, F Furuya, A Kawaguchi, M Kaneshige, J Itakura, H Fujii, T Endo, T Kobayashi
Diabetes 2011
Atelocollagen-mediated Systemic Delivery Prevents Immunostimulatory Adverse Effects of siRNA in Mammals
S Inaba, S Nagahara, N Makita, Y Tarumi, T Ishimoto, S Matsuo, K Kadomatsu, Y Takei
Molecular Therapy 2011
Induction of Noxa-mediated apoptosis by modified vaccinia virus Ankara depends on viral recognition by cytosolic helicases, leading to IRF-3/IFN-β-dependent induction of pro-apoptotic Noxa
PE Ferrer, S Potthoff, S Kirschnek, G Gasteiger, W Kastenmüller, H Ludwig, SA Paschen, A Villunger, G Sutter, I Drexler, G Häcker
PLoS pathogens 2011
The Proapoptotic Bcl-2 Protein Bax Plays an Important Role in the Pathogenesis of Reovirus Encephalitis ▿
HM Berens, KL Tyler
Journal of virology 2011
The Ribonucleotide Reductase R1 Subunits of Herpes Simplex Virus 1 and 2 Protect Cells against Poly(I · C)-Induced Apoptosis▿
F Dufour, L Bertrand, A Pearson, N Grandvaux, Y Langelier
Journal of virology 2011
Toll-like Receptor 3, RIG-I-like Receptors and the NLRP3 Inflammasome: Key Modulators of Innate Immune Responses to Double-stranded RNA Viruses
M Yu, SJ Levine
Cytokine & Growth Factor Reviews 2011
The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates
VG Chinchar, KH Yu, JK Jancovich
Viruses 2011
Oncolytic Specificity of Newcastle Disease Virus Is Mediated by Selectivity for Apoptosis-Resistant Cells▿
M Mansour, P Palese, D Zamarin
Journal of virology 2011
Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss) ▿ †
M Chang, B Collet, P Nie, K Lester, S Campbell, CJ Secombes, J Zou
Journal of virology 2011
Sensing of viral nucleic acids by RIG-I: from translocation to translation
A Schmidt, S Rothenfusser, KP Hopfner
European Journal of Cell Biology 2011
Defective NF- B Signaling in Metastatic Head and Neck Cancer Cells Leads to Enhanced Apoptosis by Double-Stranded RNA
N Umemura, J Zhu, YK Mburu, A Forero, PN Hsieh, R Muthuswamy, P Kalinski, RL Ferris, SN Sarkar
Cancer research 2011
Retinoic acid inducible gene-I, more than a virus sensor
F Liu, J Gu
Protein & Cell 2011
Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation
E Kovalcsik, K Lowe, M Fischer, A Dalgleish, MD Bodman-Smith
Cancer Immunology, Immunotherapy 2011
Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells.
Harashima N, Inao T, Imamura R, Okano S, Suda T, Harada M
Cancer Immunology, Immunotherapy 2011
Type I interferon: friend or foe?
G Trinchieri
Journal of Experimental Medicine 2010
Coexpressed RIG-I agonist enhances humoral immune response to influenza virus DNA vaccine
JM Luke, GG Simon, J Söderholm, JS Errett, JT August, M Gale, CP Hodgson, JA Williams
Journal of virology 2010
Double-stranded RNAs containing multiple IU pairs are sufficient to suppress interferon induction and apoptosis
P Vitali, AD Scadden
Nature Structural & Molecular Biology 2010
IRF-3 partners Bax in a viral-induced dance macabre
JE Vince, J Tschopp
The EMBO Journal 2010
The chase for the RIG-I ligand--recent advances
M Schlee, G Hartmann
Molecular Therapy 2010
Poly(I:C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors using EGF-polyethylene glycol-linear polyethylenimine as carrier
D Schaffert, M Kiss, W Rödl, A Shir, A Levitzki, M Ogris, E Wagner
Pharmaceutical Research 2010
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